Signature Database
COSMIC_v3.4_SBS_GRCh38
Fitting Method
Sigminer QP
Disease
Colon Adenocarcinoma
Sample
TCGA-CA-6717-01
Description
Primary Tumour
Total number of mutations is acceptable
Cosine Similarity
The similarity is great!
Summary: Since both the total number of mutations and cosine similarity of the signature analysis are acceptable, the analysis can be considered useful. Take note of the discrepancies between the reconstructed and observed profiles, if any difference between the models lie within one mutation, then the sample should be flagged
Significant Signatures: ["SBS10a","SBS10b","SBS15","SBS28","SBS37","SBS46"]
Substitution Catalogue, Reconstructed Profiles and Signatures:
The total number of mutations of a certain type ("SBS96", "ID83", "DBS78") can be found in the sample. If the total is too low then the sample may not have significant information to be considered reliable.
The reconstructed model shows the observed profile and the a model based on the significant signatures present in the sample. The cosine similarity ranges from 0 to 1 and is a measure of the likeness of the two plots and determines how well the observed model relates to the reconstruction. A low cosine similarity would mean that the observed plot may not be accurate as a result of a poor sample, few mutations or improper analysis. The discrepancy model also shows the differences between the two plots. If a single mutation has a significant proportion of the discrepancies then the sample analysis may not be reliable. As well as this, the report has a set of signatures that contribute to the sample's substitution profile. If there is a significant proportion of unassigned mutations (over 40%) then the sample provided may either be too small or that the signature may be unknown. Look at the information in the cards to confirm that the signatures are correct based on context, for example a lung cancer sample would most likely contain SBS4 which is associated with tobacco smoking.
Supplementary Details:
The supplementary details section show a box plot which shows significant data for all mutations that were tested for in the sample. The algorithm that was used to estimate the signatures contributing to this sample generated multiple solutions via bootstrapping. Signatures that had a median above a 5% threshold for a significant p-value would be considered as being part of the sample, and those signatures that were below were disregarded.
As well as this, the heatmap provides the Spearman's rank correlation coefficients between signatures across all bootstrapped solutions. This represents the signatures' contributions for the particular sample and how they correlate to each other.
Signature SBS10a/SBS10b usually generate large numbers of somatic mutations (>100 mutations per MB) and samples with these signatures have been termed hypermutators
Class: dysfunctional_dna_replication
Subclass: polymerase_mutations
Aetiology: POLE exonuclease domain mutation
Proposed Aetiology Support: Experimental confirmation
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2020 Nature
SBS10a/SBS10b usually generate large numbers of somatic mutations (>100 mutations per MB) and samples with these signatures have been termed hypermutators
Class: dysfunctional_dna_replication
Subclass: polymerase_mutations
Aetiology: POLE exonuclease domain mutation
Proposed Aetiology Support: Experimental confirmation
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2020 Nature
SBS28 has similarities to SBS17b and these two signatures can be mistaken for one another. Signature SBS28 is found in most samples with SBS10a/SBS10b where it contributes very high numbers of mutations. In contrast, SBS28 contributes much smaller number of mutations in samples lacking SBS10a/SBS10b
Class: dysfunctional_dna_replication
Subclass: polymerase_mutations
Aetiology: POLE exonuclease domain mutation
Proposed Aetiology Support: Experimental studies
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2015 Nature Genetics / Nik-Zainal et al. 2016 Nature
Signature SBS46 was found commonly in colorectal cancers from early releases of TCGA (data released prior 2013)
Class: artefact
Subclass: sequencing_artefact
Aetiology: Sequencing artifact (early releases of TCGA)
Proposed Aetiology Support: Not found in subsequence releases
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2020 Nature
SBS15 is one of seven mutational signatures associated with defective DNA mismatch repair and microsatellite instability (MSI) and is often found in the same samples as other MSI associated signatures: SBS6, SBS14, SBS20, SBS21, SBS26, and SBS44
Class: dysfunctional_dna_repair
Subclass: MMR
Aetiology: MMR deficiency
Proposed Aetiology Support: Statistical association; Experimental studies
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2013 Nature
NA
Class: unknown
Subclass: unknown
Aetiology: Unknown
Proposed Aetiology Support: Unknown
Validated in Orthogonal Techniques?: Yes
Signature Version: Mutational Signatures (v3.4 - October 2023)
Identification Study: Alexandrov et al. 2020 Nature
Unassigned
Similar Samples
The pie chart represents all of the cancer sample profiles in Signal's database (broken down by organ) that have a cosine similarity with this sample's profile that is greater than or equal to the given threshold. Lower threshold values are typically less meaningful. Below are the top 5 similar samples compared to the sample.
Disease
Colon Adenocarcinoma
Sample
TCGA-CF-A9FF-01
Description
Primary Tumour
Disease
Mesothelioma
Sample
TCGA-A2-A0T5-01
Description
Primary Tumour